Proline (Pro, P) - Structure, pKa, pI, and Codons
What is proline and what is its side chain?
Proline (Pro, P) has the side chain -(CH₂)₃- (cyclized to the alpha-amino N) - A three-carbon bridge joining the alpha carbon back to the alpha-amino nitrogen, forming a pyrrolidine ring. It is classified as nonpolar, aliphatic, carries a neutral (0) charge at pH 7, and has an isoelectric point of 6.48.
| Three-letter code | Pro |
| One-letter code | P |
| Molecular formula | C₅H₉NO₂ |
| Molecular weight | 115.13 g/mol |
| Residue mass | 97.12 Da |
| Side chain | -(CH₂)₃- (cyclized to the alpha-amino N) - A three-carbon bridge joining the alpha carbon back to the alpha-amino nitrogen, forming a pyrrolidine ring. |
| Classification | Nonpolar, aliphatic |
| pKa (alpha-COOH) | 1.99 |
| pKa (alpha-NH3+) | 10.96 |
| Isoelectric point (pI) | 6.48 |
| Charge at pH 7 | neutral (0) |
| Essentiality | Conditionally essential |
| Hydropathy (Kyte-Doolittle) | -1.6 |
| Configuration | L-form is (S) |
| Codons | CCU, CCC, CCA, CCG (4) |
Side chain
The R group of proline is -(CH₂)₃- (cyclized to the alpha-amino N). A three-carbon bridge joining the alpha carbon back to the alpha-amino nitrogen, forming a pyrrolidine ring. This is what distinguishes it from the other 19 amino acids, since all of them share the same backbone: an alpha carbon bonded to an amino group, a carboxyl group, and a hydrogen.
Ionization and isoelectric point
Proline has 2 ionizable groups: alpha-COOH (pKa 1.99), alpha-NH3+ (pKa 10.96). The isoelectric point is the pH at which the molecule carries no net charge, found by averaging the two pKa values that bracket the neutral species.
pI = (1.99 + 10.96) / 2 = 6.48
These values are for the free amino acid. Inside a folded protein, the local environment shifts them substantially.
Stereochemistry
The alpha carbon of L-proline is (S).
Genetic code
4 codons encode proline: CCU, CCC, CCA, CCG.
Features
- Secondary amine
- Helix breaker
MCAT notes
- The only amino acid with a secondary amine - its side chain loops back onto the alpha nitrogen to form a pyrrolidine ring.
- It has no backbone N-H, so it cannot donate the hydrogen bond that stabilizes an alpha helix. This makes it the classic helix breaker.
- X-Pro peptide bonds show an appreciable cis population, unlike every other residue.
- Hydroxylated to hydroxyproline in collagen by prolyl hydroxylase, a vitamin C dependent enzyme. Deficiency causes scurvy.
Proline and glycine break helices - for opposite reasons (too rigid vs too floppy).
Interactive 3D structure with the R group isolated, a titration curve with a live pH cursor, and flashcards for all 20 amino acids.
View proline in 3D